The effect of short-term hypoxic exposure on metabolic gene expression.

The long-term effect of hypoxia is to decrease both the production and use of ATP and thus decrease the reliance on mitochondrial oxidative energy production. Yet, recent studies include more immediate affects of hypoxia on gene expression and these data suggest the maintenance of mitochondrial function. To better understand the short-term physiological response to hypoxia, we quantified metabolic mRNA expression in the heart ventricles and livers of the teleost fish Fundulus grandis exposed to partial oxygen pressure of 2.8 kPa (-13.5% air saturation).Twenty-eight individuals from a single population were exposed to hypoxia for 0, 4, 8, 12, 24, 48, and 96  hr. Liver and cardiac tissues were sampled from the same individuals at 0-48  hr. At 96  hr, only cardiac tissue was assayed. Gene expression was significantly different (ANOVA, P < 0.05) for 17 of 226 metabolic genes (7.5%) in cardiac tissue and for 20 of 256 (7.8%) metabolic genes in hepatic tissue. For the two tissues examined in this study, the maximum response occurred at different times. For cardiac tissue, using Dunnett's post hoc test, most of these significant differences occurred at 96  hr of exposure. For liver, all but one significant difference occurred at 4  hr. Surprisingly, too many (relative to random expectations) of the genes with significant increase in mRNA are involved in the oxidative phosphorylation pathway: 44% of the significant genes at 96  hr in the heart and 33% of the significant genes at 4  hr in the liver are involved in the oxidative phosphorylation pathway. These data indicate that there are tissue-specific differences in the timing of the response to hypoxia, yet both cardiac and hepatic tissues have increases in mRNA that code for enzyme in the oxidative phosphorylation pathway. If these changes in mRNA produce a similar change in protein, then these data suggest that the initial response to hypoxia involves an increase in the oxidative pathway potentially as a mechanism to maintain ATP production.